Fossil records suggest many cataclysmic events in evolution of the phylum Bryozoa and a great number of ancient members have become extinct. The 4,000 plus species that presently exist, represent a very competitive group of animals with highly developed survival mechanisms. Perhaps due to their generally pedestrian appearance and likelihood of being mistaken for seaweeds, hydroids or corals, these otherwise fascinating "moss animals" have received little biological and chemical study. Because of our earlier observations that extracts of the marine bryozoan Bugula neritina (Linnaeus) exhibited exceptional antineoplastic activity (100% life extension) against the U.S. National Cancer Institute murine P388 lymphocytic leukemia (PS system), we undertook an extensive investigation of such constituents. Fourteen years later we were able to report the isolation and x-ray crystal structure of bryostatin 1, the first member of what we hope to be a very potent (low dose) class of new antitumor substances. Subsequently, we discovered other bryostatins of the bryostatins 1 and 4 types which were found to possess remarkable (PS inhibition to 10 .mu.g/kg dose levels) antineoplastic activity. In the same period, other bryozoans were found to contain new pyrrole, indole, quinoline, and purine marine alkaloids with some displaying antibacterial, antifungal, or antialgal activity while others inhibited the division of fertilized sea urchin egg cells.
In the continuing effort to locate and define various natural and synthesizable substances for treatment of one or more varieties of cancer, research chemists continue to look at natural flora and fauna in an attempt to isolate and identify new substances which exhibit antineoplastic activity while substantially minimizing, if not totally eliminating, some of the severe side effects accompanying known chemotherapeutic agents.
It is in the further pursuit of these goals that marine species heretofore ignored are now being examined to determine whether they contain constituents which when isolated, will exhibit antineoplastic activity.
Accordingly, a principal object of the present invention is to provide new agents useful in the retardation or remission of one or more types of cancer.
Another object of the present invention is to provide methods and procedures for isolating antineoplastic substances from marine plant life in a form whereby they may be readily and usefully employed in the therapeutic treatment and management of one or more types of cancer which occur in human hosts.
A further object of the present invention is the provision of unique means and methods for isolating and identifying new 20-desoxybryostatins from marine sources.
These and still further objects as shall hereinafter appear are readily fulfilled by the present invention in a remarkably unexpected manner as will be readily discerned from the following detailed description of an exemplary embodiments thereof.